Pifithrin-α (PFTalpha) is a reversible inhibitor of p53-mediated apoptosis and p53-dependent gene transcription such as cyclin G, p21/waf1, and mdm2 expression. It prevents p53-mediated apoptosis induced by cytotoxic compounds in C8 cells at 10 μM and in human umbilical vein endothelial cells at 30 μM. Pifithrin-α enhances cell survival after genotoxic stress such as UV irradiation and treatment with cytotoxic compounds including doxorubicin, etopoxide, paclitaxel, and cytosine-β-D-arabinofuranoside. Pifithrin-α protects mice from lethal whole body γ-irradiation without an increase in cancer incidence. Pifithrin-α can also protect cells from DNA damage-induced apoptosis by a p53-independent mechanism that might involve cyclin D1. In addition to p53, PFTalpha can suppress heat shock and glucocorticoid receptor signaling but has no effect on nuclear factor-kappaB signaling. Pifithrin-α (PFTalpha) reduces activation of heat shock transcription factor (HSF1) and increases cell sensitivity to heat. Moreover, Pifithrin-α reduces activation of glucocorticoid receptor and rescues mouse thymocytes in vitro and in vivo from apoptotic death after dexamethasone treatment.
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
|Solubility||DMSO 60 mg/mL|
The p53 inhibitor pifithrin-α can stimulate fibrosis in a rat model of ischemic acute kidney injury.
Dagher PC, et al. Am J Physiol Renal Physiol. 2012 Jan 15;302(2):F284-91. PMID: 22049400.
Pifithrin-alpha inhibits p53 signaling after interaction of the tumor suppressor protein with hsp90 and its nuclear translocation.
Murphy PJ, et al. J Biol Chem. 2004 Jul 16;279(29):30195-201. PMID: 15145929.
p53 inhibitor pifithrin alpha can suppress heat shock and glucocorticoid signaling pathways.
Komarova EA, et al. J Biol Chem. 2003 May 2;278(18):15465-8. PMID: 12637507.
A chemical inhibitor of p53 that protects mice from the side effects of cancer therapy.
Komarov PG, et al. Science. 1999 Sep 10;285(5434):1733-7. PMID: 10481009.
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